Abstract

Small nuclear ribonucleoproteins (snRNPs) are protein–ribonucleic acid (RNA) complexes defined by a core noncoding RNA of approximately 100–600 nucleotides and tightly bound proteins that together accumulate
in the nucleus. The snRNPs are best known for their role in RNA splicing complexes, including U1, U2, U4, U5 and U6 snRNPs
found in the spliceosome. Additional snRNPs are functionally diverse, but in many cases the RNA component of snRNPs can base‐pair
with a substrate for precise alignment and possible catalysis. The U7 snRNP directs 3′‐end mRNA formation for histone transcripts,
and the 7SK snRNP regulates transcription. Two special groups of snRNPs, small nucleolar RNPs (snoRNPs) and small Cajal‐body RNPs (scaRNPs), are restricted to their named subnuclear compartments in order to direct post‐transcriptional modification of ribosomal
and splicing RNAs, respectively. Certain herpesviruses express high levels of novel snRNPs involved in the regulation of gene
expression. Due to their important biological roles, there are many diseases associated with snRNPs.

Key Concepts:

The snRNPs are small nuclear ribonucleoprotein particles, a class of dynamic RNA–protein complexes that accumulate in the
nucleus.

Major and minor splicing snRNPs form super‐complexes (spliceosomes) that direct the precise splicing of messenger RNAs.

In the special process of trans‐splicing, splice leader (SL) snRNPs donate RNA to the ends of transcripts.

Two groups of snRNPs are singled out for specific subnuclear localisation: small nucleolar and small Cajal‐body associated
(sno/scaRNPs) direct methylation and pseudouridylation of splicing and ribosomal RNAs.

Some mammalian herpesviruses express viral snRNPs, which have enigmatic and complex functions in gene regulation.

Several diseases including lupus present autoantibody production of antibodies directed at snRNP‐affiliated proteins such
as Sm, Lsm and La.

Most snRNPs have been affiliated with diseases and are therefore promising biomarkers for diagnosis and prognosis.

Secondary structural features of the U1 and U11 snRNAs are similar. (a) Secondary structural predictions indicate a remarkably similar overall four‐hairpin fold for both U1 and U11 in spite of extensive differences in primary sequence. The 5′ splice site (red boxes) and Sm protein (black boxes) binding sequences are in approximately the same place in both RNAs. The consensus sequence for Sm protein binding is noted on U1. (b) Both snRNAs have a 5′ TMG cap (depicted as a triangle in (a)).

Figure 2.

Schematic representation of the U7 snRNP directing histone mRNA 3′ end formation. The U7 snRNA has a 5′ TMG cap (triangle) and Sm/Lsm protein ring (light blue). Stem‐loop binding protein (SLBP) binds a specific hairpin near the 3′ end of the histone mRNA (purple) and interacts with the zinc finger protein (ZFP100) bridging protein (green), which also binds Lsm11 (light blue). A region of the U7 snRNA known as the HDE base‐pairs to the histone pre‐mRNA substrate (red box). The histone mRNA is cleaved in the denoted location (red arrow), for which the CPSF‐73 endonuclease is required (dark blue).

Figure 3.

Cartoon structure of the human 7SK snRNA based on a model for structural pairing predicted by conservation of primary sequences across many species. Coloured areas highlight portions of the snRNA that directly or indirectly facilitate protein binding in the snRNP. A large stem loop is the binding site for the HEXIM proteins (blue). To be fully associated with 7SK snRNP, P‐TEFb requires a hairpin near the 3′ end of the snRNA (purple) and makes key protein–protein contacts with HEXIM. The 3′ end (yellow) is comprised of a stretch of uridine residues that are initially bound by the La protein, which is replaced by Larp7 after post‐transcriptional modifications of the end. MePCE methylates the 5′ end of the 7SK snRNA (green). When P‐TEFb and HEXIM dissociate from the 7SK snRNP complex, they are replaced by heterogeneous RNP particle (hnRNP) proteins, which bind in two regions (open circles), including a stretch of seven base pairs that anchors the 5′ end near the 3′ end (Peterlin et al., ; Marz et al., ).

Figure 4.

Chemical modifications of RNA directed by snoRNAs. (a) The process of 2′‐O‐ribose methylation of RNA is the addition of a methyl group (red) via the oxygen connected to the 2′ ribose carbon of a specific nucleotide (attached phosphate groups and bases remain unaltered). (b) Pseudouridylation is the isomerisation of uracil into pseudouracil while the sugar/phosphate backbone remains unchanged. Altered chemical substituents are highlighted (red). (c) Schematic secondary structure of a representative class C/D snoRNA, which contains class‐specific conserved sequences (boxes C and D, blue and green). Unique guide sequences base‐pair with target rRNAs (red). A methyl group is added to the rRNA residue base‐paired to the fifth position upstream from box D or D’. (d) Box H/ACA snoRNAs adopt a double hairpin structure. Base‐pairing of an rRNA to an internal loop in the snoRNA results in the pseudouridylation (Nψ) of an unpaired rRNA U residue (usually 14–16 nucleotides from the H or ACA box).

Figure 5.

Viral snRNPs. (a) The predicted secondary structures of EBV EBERs 1 and 2 depict hairpins, some of which are binding sites for proteins. Ribosomal protein pRL22 binds to three of the stem loops in EBER1 (green). The La protein binds a U‐rich track in both EBERs (purple). The PKR protein (in vitro) and nucleolin have been shown to bind EBERs 1 and 2, respectively, though their binding sites have not been mapped. (b) HSUR1 is one of the seven snRNAs expressed in H. saimiri. The HSUR1 snRNP has a 5′ TMG cap (triangle) and includes a ring of host Sm proteins (light blue). HSUR1 base‐pairs to two human microRNAs (miR‐27 and miR‐142‐3p) in the locations shown (yellow).

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